Korean J Anesthesiol.  2012 Sep;63(3):253-259. 10.4097/kjae.2012.63.3.253.

Dexmedetomidine-induced contraction of isolated rat aorta is dependent on extracellular calcium concentration

• Ok SH
• Bae SI
• Shim HS
• Sohn JT

• KMID: 2236276
• DOI: http://doi.org/10.4097/kjae.2012.63.3.253

Abstract

BACKGROUND
Dexmedetomidine is a highly selective alpha2-adrenoceptor agonist that is widely used for sedation and analgesia during the perioperative period. Intravenous administration of dexmedetomidine induces transient hypertension due to vasoconstriction via the activation of the alpha2-adrenoceptor on vascular smooth muscle. The goal of this in vitro study is to investigate the calcium-dependent mechanism underlying dexmedetomidine-induced contraction of isolated endothelium-denuded rat aorta.
METHODS
Isolated endothelium-denuded rat thoracic aortic rings were suspended for isometric tension recording. Cumulative dexmedetomidine concentration-response curves were generated in the presence or absence of the following inhibitors: alpha2-adrenoceptor inhibitor rauwolscine; voltage-operated calcium channel blocker verapamil (5 x 10(-7), 10(-6) and 5 x 10(-5) M); purported inositol 1,4,5-trisphosphate receptor blocker 2-aminoethoxydiphenylborate (5 x 10(-6), 10(-5) and 5 x 10(-5) M); phospholipase C inhibitor U-73122 (10(-6) and 3 x 10(-6) M); and store-operated calcium channel inhibitor gadolinium chloride hexahydrate (Gd3+; 5 x 10(-6) M). Dexmedetomidine concentration-response curves were also generated in low calcium concentrations (1 mM) and calcium-free Krebs solution.
RESULTS
Rauwolscine, verapamil, and 2-aminoethoxydiphenylborate attenuated dexmedetomidine-induced contraction in a concentration-dependent manner. Low calcium concentrations attenuated dexmedetomidine-induced contraction, and calcium-free Krebs solution nearly abolished dexmedetomidine-induced contraction. However, U-73122 and Gd3+ had no effect on dexmedetomidine-induced contraction.
CONCLUSIONS
Taken together, these results suggest that dexmedetomidine-induced contraction is primarily dependent on extracellular calcium concentrations that contribute to calcium influx via voltage-operated calcium channels of isolated rat aortic smooth muscle. Dexmedetomidine-induced contraction is mediated by alpha2-adrenoceptor stimulation. Dexmedetomidine-induced contraction appears to be partially mediated by calcium release from the sarcoplasmic reticulum.

Keyword

Aorta; Calcium; Contraction; Dexmedetomidine; Voltage-operated calcium channel

MeSH Terms

Administration, Intravenous
Analgesia
Animals
Aorta
Calcium
Calcium Channels
Contracts
Dexmedetomidine
Estrenes
Gadolinium
Hypertension
Inositol 1,4,5-Trisphosphate
Isotonic Solutions
Muscle, Smooth
Muscle, Smooth, Vascular
Perioperative Period
Pyrrolidinones
Rats
Sarcoplasmic Reticulum
Type C Phospholipases
Vasoconstriction
Verapamil
Yohimbine
Calcium
Calcium Channels
Dexmedetomidine
Estrenes
Gadolinium
Inositol 1,4,5-Trisphosphate
Isotonic Solutions
Pyrrolidinones
Type C Phospholipases
Verapamil
Yohimbine